Successful catheter cryoablation of Hisian ectopy using 2 new diagnostic criteria based on unipolar and bipolar recordings of the His electrogram

We describe the case of a 61-year-old woman who underwent successful catheter cryoablation of a symptomatic Hisian ectopy. Diagnosis was based on features of the HV interval assessed from a bipolar recording during mapping. The location of the arrhythmic focus was identified using simultaneous unipolar and bipolar recordings of the His electrogram. This case report highlights the use of 2 new criteria for the diagnosis and mapping of Hisian ectopy, and the successful use of cryothermia for the ablation of extrasystoles arising from the His bundle.     

The batrachotoxin receptor on the voltage-gated sodium channel is guarded by the channel activation gate

Batrachotoxin (BTX), from South American frogs of the genus Phyllobates, irreversibly activates voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In this study, we introduced a series of mutations at this site in the Na(v)1.3 sodium channel, expressed wild-type and mutant channels in Xenopus laevis oocytes, and examined their sensitivity to BTX using voltage clamp recording. We found that substitution of either alanine or isoleucine strongly reduced channel sensitivity to toxin, whereas cysteine, tyrosine, or tryptophan decreased toxin action only modestly. These data suggest an electrostatic ligand-receptor interaction at this site, possibly involving a charged tertiary amine on BTX. We then used a mutant channel (mutant F1710C) with intermediate toxin sensitivity to examine the properties of the toxin-receptor reaction in more detail. In contrast to wild-type channels, which bind BTX almost irreversibly, toxin dissociation from mutant channels was rapid, but only when the channels were open, not when they were closed. These data suggest the closed activation gate trapped bound toxin. Although BTX dissociation required channel activation, it was, paradoxically, slowed by strong membrane depolarization, suggesting additional state-dependent and/or electrostatic influences on the toxin binding reaction. We propose that BTX moves to and from its receptor through the cytoplasmic end of the open ion-conducting pore, in a manner similar to that of quaternary local anesthetics like QX314.     

Pain relief in major trauma patients: an Israeli perspective

BACKGROUND: The pain of major trauma patients remains often unrelieved while in the emergency department. Our objective was to examine pain management in several trauma units, and to evaluate the impact of implementation of a trauma pain management protocol. METHODS: Current status was evaluated from questionnaires filled by trauma unit personnel of nine medical centers. In one, a pain management protocol was introduced. Staff and patients evaluated pain management before and after the protocol was instituted. RESULTS: About 80% of staff respondents from various centers were not aware of guidelines for pain management in trauma. The belief that pain assists diagnosis was the main reason (78.6%) for withholding analgesia. Large variability existed on what contraindicates analgesia, with the majority withholding analgesia in abdominal and multiple injuries. When administered, analgesia was delayed, and most commonly intramuscular meperidine was given. After the protocol's implementation, the personnel's awareness of analgesia increased, and consequently it was administered earlier and to more patients, mostly as intravenous morphine. Patients appreciated the timely analgesia (38% after vs. 14% before, p = 0.01), with fewer receiving none. Analgesia was considered beneficial by more patients (70% after vs. 23% before, p < 0.001), and enhanced cooperativity with personnel (p < 0.001). This was reflected in increased overall satisfaction with pain relief during the entire hospitalization. CONCLUSION: The importance of pain management protocols in major trauma was demonstrated by the response of personnel and patients.     

Hand immersion in cold water alleviating physiological strain and increasing tolerance to uncompensable heat stress

The current study examines the use of hand immersion in cold water to alleviate physiological strain caused by exercising in a hot climate while wearing NBC protective garments. Seventeen heat acclimated subjects wearing a semi-permeable NBC protective garment and a light bulletproof vest were exposed to a 125 min exercise-heat stress (35 degrees C, 50% RH; 5 km/h, 5% incline). The heat stress exposure routine included 5 min rest in the chamber followed by two 50:10 min work-rest cycles. During the control trial (CO), there was no intervention, whilst in the intervention condition the subjects immersed their hands and forearms in a 10 degrees C water bath (HI). The results demonstrated that hand immersion in cold water significantly reduced physiological strain. In the CO exposure during the first and second resting periods, the average rectal temperature (T (re)) practically did not decrease. With hand immersion, the mean (SD) T (re) decreased by 0.45 (0.05 degrees C) and 0.48 degrees C (0.06 degrees C) during the first and second rest periods respectively (P < 0.005). Significant decreases in skin temperature, sweat rate, heart rate, and heat storage was also noted in the HI vs. the CO trials. Tolerance time in the HI exposure were longer than in the CO exposure (only 12 subjects in the CO trial endured the entire heat exposure session, as opposed to all 17 subjects in the HI group). It is concluded that hand immersion in cold water for 10 min is an effective method for decreasing the physiological strain caused by exercising under heat stress while wearing NBC protective garments. The method is convenient, simple, and allows longer working periods in hot or contaminated areas with shorter resting periods.     

Motivation,cohesion, satisfaction,and their relation to stress fracture among female military recruits

The purpose of this study was to compare ratings of motivation, satisfaction, self-efficacy, and cohesion between male and female soldiers undergoing basic training (BT) in a gender-integrated unit and to study whether the ratings differ in a subgroup of women who suffered stress fractures (SF) during the course of training. Data were collected from 3 different companies of an integrated combat unit using questionnaires that were completed by 41 male and 160 female soldiers (age 18.5 +/- 0.4 years) at 3 phases during their BT (0, 2, and 4 months). In these questionnaires, the subjects were asked to evaluate their motivation, cohesion, satisfaction and self-efficacy. The presence or absence of bone overuse injuries was assessed by magnetic resonance imaging (MRI) or bone scintigraphy (BS). In addition to comparing parameters between females and males, female soldiers who sustained SF during BT (n = 18) were analyzed as a separate sub-group (FSF). In general, females in a gender-integrated combat unit were more motivated and satisfied with their service than their male counterparts. Overall, the stress fractures were associated with lower ratings of motivation, self-efficacy, and satisfaction expressed by the FSF sub-group.     

The many faces of peroxisomal disorders: Lessons from a large Arab cohort

Defects in the peroxisomes biogenesis and/or function result in peroxisomal disorders. In this study, we describe the largest Arab cohort to date (72 families) of clinically, biochemically and molecularly characterized patients with peroxisomal disorders. At the molecular level, we identified 43 disease-causing variants, half of which are novel. The founder nature of many of the variants allowed us to calculate the minimum disease burden for these disorders in our population ~1:30 000, which is much higher than previous estimates in other populations. Clinically, we found an interesting trend toward genotype/phenotype correlation in terms of long-term survival. Nearly half (40/75) of our peroxisomal disorders patients had documented survival beyond 1 year of age. Most unusual among the long-term survivors was a multiplex family in which the affected members presented as adults with non-specific intellectual disability and epilepsy. Other unusual presentations included the very recently described peroxisomal fatty acyl-CoA reductase 1 disorder as well as CRD, spastic paraparesis, white matter (CRSPW) syndrome. We conclude that peroxisomal disorders are highly heterogeneous in their clinical presentation. Our data also confirm the demonstration that milder forms of Zellweger spectrum disorders cannot be ruled out by the “gold standard” very long chain fatty acids assay, which highlights the value of a genomics-first approach in these cases.